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We searched whether the accumulation of Advanced Glycation End-products (AGEs), reflected by the skin autofluorescence (SAF), could predict diabetic foot ulcers (DFUs) during the long-term follow-up of people with type 1 diabetes. During year 2009, we measured the SAF with an AGE-Reader in 206 subjects with type 1 diabetes. DFU and amputations were registered during the 10 following years. The relation between the SAF and later DFU was analyzed by Cox model regression, adjusted for vascular risk factors. The 206 participants were mainly men (55.8%), 51 ± 15 years old, with a 22 ± 13 years diabetes duration. Twelve subjects presented a DFU. Their SAF were higher: 2.61 ± 0.89 AU vs 2.11 ± 0.53 for the others (p = 0.003), related to the risk of DFU (OR:3.69; 95% CI: 1.06–12.79) after adjustment for age, gender, diabetes duration, initial HbA1c, arterial hypertension, history of smoking, blood lipids and use of a statin. Five subjects were amputated, also related to the initial SAF: OR: 11.28 (95% CI: 1.76–79.97) after adjustment for age, gender, duration of diabetes, and HbA1c. The SAF has already been related to diabetic neuropathy and peripheral arterial disease. It predicts DFU in type 1 diabetes, which suggests that AGEs play a role in this highly specific and feared complication.

KRAS (Kirsten Rat Sarcoma) is the most common oncogenic mutation detected in patients with non-small cell lung cancer (NSCLC). However, the role of KRAS as either a prognostic factor or predictive factor (modifier of treatment effects) in NSCLC is not well established at this time. This systematic literature review (SLR) and meta-analysis synthesized the available evidence regarding the role of KRAS mutation as a predictive factor and/or prognostic factor of survival and response outcomes in patients with advanced/metastatic (stage IIIB-IV) NSCLC. Relevant clinical trials and observational studies were identified by searching MEDLINE, Embase and Cochrane Register of Controlled Trials. Meta-analyses were performed using data extracted from multivariable and univariable analyses from clinical studies to assess the empirical evidence of KRAS mutation status as a prognostic or/and predicitive factor. 43 selected studies were identified by the SLR and included in this meta-analysis. Pairwise meta-analyses of hazard ratios (HRs) reported in randomized controlled trials (RCTs) did not demonstrate a significant prognostic effect of mutant KRAS on overall survival (OS) (HR=1.10; 95% CI [0.88, 1.38]) or progression free survival (PFS) (HR=1.03; 95% CI [0.80, 1.33]). However, when conducting meta-analyses on HRs reported in observational studies, a statistically significant negative prognostic effect of mutant KRAS was observed (OS HR=1.71; 95% CI [1.07, 2.84]; PFS HR=1.18; 95% CI [1.02, 1.36]). Meta-analyses of objective response rate (ORR) in RCTs demonstrated a negative prognostic effect of mutant KRAS (RR=0.38; 95% CI [0.16, 0.63]). Limited data were available to evaluate the role of KRAS mutation as a predictive factor. In conclusion, this research offers evidence that KRAS mutation may be a negative prognostic factor for survival and response outcomes in patients with advanced/metastatic NSCLC, but further research is needed to address conflicting results on the importance of KRAS mutations as a predictive factor.

CancerChatCanada is a pan-Canadian initiative with a mandate to make professionally led cancer support groups available to more people in Canada. Although online support groups are becoming increasingly popular, little is known about therapist-led, synchronous groups using live chat. The purpose of this study was to generate a rich descriptive account of communication experiences in CancerChatCanada groups and to gain an understanding of processes associated with previously-reported benefits. We used interpretive description to analyze interview segments from 102 patients, survivors and family caregivers who participated in CancerChatCanada groups between 2007 and 2011. The analysis yielded four inter-related process themes (Reaching Out From Home, Feeling Safe, Emotional Release, and Talking With Text) and one outcome theme (Resonance and Kinship). The findings extend previous research about text-only online support groups and provide novel insights into features of facilitated, live chat communication that are valued by group members.

This initial study examined a therapist-led, synchronous, online support group (OSG) with psycho-education (OSG + E) compared to self-help psycho-education (E). The study aims were to examine proof of concept—feasibility, acceptability, and usefulness—and to hone methods for a formal RCT. One hundred five young breast cancer survivors (

Cytochrome P450cam (CYP101) catalyzes the oxidation of D(+)-camphor at the 5 position. The enzyme couples the reduction of dioxygen to the oxidation of the substrate. To transfer electrons from the reductant (NADH) to the cytochrome, two additional proteins are required. These are putidaredoxin (PdX) and putidaredoxin reductase (PdR). We have chemically linked a form of PdX with a histidine tag at the C-terminus to the P450. To accomplish this, we have modified cysteine 334 on P450 with a bipyridinyl group, and co-ordinated the C-terminal histidine tag of PdX by the addition of Ni2+ or Ru3+. The Ru3+ complex was the most stable. The non-linked system gave mostly 5-ketocamphor, a product of two consecutive hydroxylations, and H2O2, a product of 2-electron uncoupling. The Ni2+ complex gave both 5-exo-hydroxycamphor and 5-ketocamphor, but it also uncoupled. The Ru3+ complex gave a single product (5-exo-hydroxycamphor) and did not uncouple at the optimal PdR concentration. Our results are consistent with othe...

Background: Professional-led cancer support groups can improve quality of life and address unmet needs, but most Canadians affected by cancer do not have access to or do not make use of cancer support groups. A collaborative interdisciplinary team developed, operated, and evaluated Internet-based, professional-led, live-chat support groups (osgs) for cancer patients, caregivers, and survivors across Canada. Objective: Our study aimed to report participant and participation characteristics in the pan-Canadian initiative known as CancerChatCanada, and to understand participant perspectives about the quality of communication and professional facilitation, overall satisfaction, and psychosocial benefits and outcomes. Methods: Participants in osgs provided informed consent. Participant and participation characteristics were gathered from program data collection tools and are described using frequencies, means, and chi-squares. Patient, survivor, and caregiver perspectives were derived from 102 telephone interviews conducted after osg completion and subjected to a directed qualitative content analysis. Results: The 55 professional-led osgs enrolled 351 participants from 9 provinces. More than half the participants came from rural or semirural areas, and more than 84% had no received previous cancer support. The attendance rate was 75%, the dropout rate was 26%, and 80% of participants were satisfied or very satisfied. The convenience and privacy of osgs were benefits. Meaningful communication about important and difficult topics, kinship and bonding with others, and improved mood and self-care were perceived outcomes. Conclusions: Our results demonstrate that this collaborative initiative was successful in increasing reach and access, and that pan-Canadian, professional-led osgs provide psychosocial benefit to underserved and burdened cancer patients, survivors, and family caregivers.

Canada is a pioneer in remote cancer care delivery to underserved populations, however, it is trailing behind on policies that would support clinicians in providing care using distance technologies. The current policy framework is disjointed, and discussions by professional boards about online jurisprudence associated with licensure appear to be regressive. We hope that by addressing the discrepancies in interjurisdictional practice and focusing on the key issue of &ldquo, where therapy resides,&rdquo, we will be able to nudge dialogue and thinking closer toward the reasoning and recommendations of national telehealth organizations. We present this discussion of jurisdictional issues and e-health practice in the context of a pan-Canadian online support program developed for cancer patients and family members. Although the present paper uses online support groups as a springboard to advocate for e-health, it ultimately addresses a broader audience: that of all Canadian health care stakeholders.

The most recognized activity of P450cam is the oxidation of the unactivated C-H bond at C-5 of D (+)-camphor to an alcohol moiety. This hydroxylation reaction has few counterparts in chemical synthesis; hence, the application of cytochrome P450cam for industrial purposes has practical potential. P450¬cam requires a carefully orchestrated reaction cycle, which includes two electron transfer partners: putidaredoxin (Pdx) and putidaredoxin reductase (Pdr). Studies have shown that Pdx plays an essential role in electron transfer and in controlling key steps in the catalytic cycle. In this thesis, the multiple-component system dependency of P450cam was addressed by chemically linking P450cam to Pdx. The linker bridging the two proteins was either a 4-carbon or 7-carbon saturated alkyl group with a functional bipyridyl anchor. This linker was chemically attached to a cysteine residue on the surface of P450cam. The histidine groups on the C-terminus of Pdx and the bipyridyl anchor on P450cam tethered the two proteins together via a coordination bridge with a metal (Ni2+ or Ru3+). The new entities showed reasonable stability and reactivity, provided a framework that improved the stability of Pdx, and did not exhibit uncoupling. In order to study the product profile of cytochrome P450cam¬ upon catalysis, a set of standards was required. The second objective of my thesis was the synthesis and characterization of the different compounds metabolized by P450cam, namely, 5-ketocamphor, 5-exo-hydroxycamphor, 5-exo-hydroxyborneol and 5-exo-hydroxyisoborneol. They were useful as standards to follow the conversion pathways of bicyclic metabolites by Pseudomonas putida’s enzymes in vivo and the activity of the linked system in vitro. In the last part of this thesis, the newly discovered actvities of cytochrome P450cam were investigated. Under high oxygen, the P450cam system over-oxidizes D (+)-camphor to (+)-5-ketocamphor by a double hydroxylation at C-5 on the bicyclic skeleton. Moreover, under low oxygen and reducing conditions, the P450cam system catalyzes the reduction of the 2-keto group of D (+)-camphor or (+)-5-exo-hydroxycamphor to (+)-borneol or (+)-5-exo-hydroxyborneol respectively. Subsequently, it was shown that Pdr enhances the reduction reaction under anoxic conditions and that the hydrogen that is installed at C-2 comes from water.